Here we show that pemetrexed-treated mesothelioma cells undergo accelerated senescence. This is characterized by the secretion of proinflammatory and mitogenic cytokines, reminiscent of an SASP ...(senescence-associated secretory phenotype). Conditioned media from senescent MPM (malignant pleural mesothelioma) cells trigger the emergence of EMT (epithelial-to-mesenchymal)-like, clonogenic and chemoresistant cell subpopulations, expressing high levels of ALDH (aldehyde dehydrogenase) activity (ALDH(bright) cells). We show by fluorescence-activated cell sorting of purified ALDH(bright) and ALDH(low) cells, that both cell-autonomous and cell-non-autonomous mechanisms converge to maintain the SASP-induced, EMT-like cell subpopulations. Chemoresistant ALDH(bright) cells exist within primary MPM specimens and enrichment for ALDH(bright) cells correlates with an earlier tumor onset into NOD/SCID mice. We show that RAS(v12) expression induces SASP-like changes in untransformed human mesothelial cells, and that p53 ablation increases the effect of RAS(v12) expression. We identify STAT3 activation as a crucial event downstream to SASP signaling. In fact, small hairpin RNA-mediated ablation of STAT3 deeply attenuates the induction of EMT genes and the increase of ALDH(bright) cells induced by SASP-cytokines. This strongly affects the chemoresistance of MPM cells in vitro and leads to anticancer effects in vivo.
Purpose
Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational ...study was to assess adherence in r-hGH patients treated with the easypod
™
, an electronic, fully automated injection device designed to track the time, date and dose administered.
Methods
Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint—adherence to treatment—was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod
™
, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined.
Results
The easypod
™
data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0–V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels.
Conclusions
The injection-recording system and other characteristics of easypod
™
could enhance the ability of physicians to monitor adherence to r-hGH treatment.
Purpose
The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the ...study was to explore the association of different proportions of fat and carbohydrates of the diet—within the ranges recommended by different guidelines—with metabolic risk factors.
Methods
We studied 1785 people with type 2 diabetes, aged 50–75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured.
Results
Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (
p
< 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (
p
< 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake.
Conclusions
In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.
Background
With the use of non-objective measurement, adherence to growth hormone (GH) therapy has been reported suboptimal in a large proportion of patients, and poor adherence has been shown to ...affect short-term growth response in patients receiving GH treatment.
Objective
The Easypod™ electronic device allows objective measurement of adherence. In this study, we report 3-year prospective adherence data of the Italian cohort of naïve GH deficient (GHD) children extrapolated from the Easypod Connect Observational Study (ECOS) database.
Patients and methods
Seventy-three GHD children naïve to GH treatment were included in the analysis. 22 Italian centers participated in the study.
Results
Mean adherence rate was consistently above 85% across the 3-year observation period. Particularly, mean adherence was 88.5%, 86.6%, and 85.7% after 1, 2 and 3 years, respectively. Mean (± SD) height-SDS increase after the first year was 0.41 (± 0.38).
Conclusions
The majority of naïve GHD children starting GH treatment with Easypod maintained an adherence rate > 85% up to 3 years. Easypod is a useful tool to follow-up patients’ adherence allowing timely intervention to improve optimal treatment for these patients.
Abstract Background and aims Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the ...quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. Methods and results We studied 2573 people, aged 50–75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. Conclusions Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.
Background: Electrochemotherapy (ECT) couples the administration of anticancer drugs with the delivery of electric pulses that increase the drug uptake through the cell membranes, resulting in an ...improved efficacy.
Hypothesis: To evaluate the tolerability and efficacy of cisplatin (CDDP) as an ECT agent to prevent recurrence of incompletely resected mast cell tumors (MCTs).
Animals: Thirty‐seven dogs.
Methods: Prospective study recruiting dogs with incompletely excised MCTs as confirmed by surgeon and pathology reports. After debulking, the tumor bed and margins were infiltrated with CDDP, and then exposed to trains of biphasic electrical pulses under sedation. Five minutes after the injection of the chemotherapy agent, sequences of 8 biphasic pulses lasting 50 + 50 μs each, were delivered in bursts of 1,300 V/cm for sclerosed and of 800 V/cm for exposed lesions, with caliper or needle array electrodes, respectively. A second session was performed 1 or 2 weeks later based on clinical considerations.
Results: The treatment was well tolerated with minimal adverse effects. Twenty‐nine dogs had no evidence of recurrence over the 6‐year study period, 6 had tumor recurrence, 1 died of multiple cutaneous MCTs, and 1 died of unrelated causes. The estimated median time to recurrence was 1,200 days. Recurrence was not observed among the long‐term (>1 year) treated dogs.
Conclusions and Clinical Importance: ECT with CDDP appears effective in the treatment of incompletely resected MCT in dogs and could be a useful addition to the current options based on its low cost, limited toxicity, and ease of administration.
A 10-year-old male intact Corso dog was referred for lameness and for a large neoplasm affecting the right foreleg. Physical examination of the patient revealed a 5 x 5 x 3 cm mass in the distal ...right foreleg. Histopathology was consistent with a diagnosis of appendicular osteosarcoma. The staging process found no evidence of metastasis. Because of the large size of the patient, the owners elected to treat their dog with antiresorptive therapy. The patient was treated with an infusion of zoledronic acid every 28 days. The tumour remained stable for 16 months and the lameness of the dog greatly improved. At that time, the patient returned for evaluation of a large rapidly growing prescapular mass. Biopsy confirmed lymph node metastasis and the dog was euthanased. Zoledronic acid showed remarkable palliation in our patient and possibly anti-tumour action and warrants further investigation.
The regioselective synthesis of fluorescent oligothiophene isothiocyanates is described. The isothiocyanates were reacted with bovine serum albumin (BSA) following standard procedures and the optical ...properties of the oligothiophene-BSA conjugates were analyzed as a function of oligomer concentration, time, and irradiation power. The oligothiophene-BSA conjugates were chemically very stable and their photoluminescence characteristics persisted unaltered for several months. Photoluminescence data relative to the conjugate of an oligothiophene-S,S-dioxide isothiocyanate with monoclonal anti-CD8 antibody are reported. No fluorescence quenching was observed following the binding of the isothiocyanate to the antibody and the conjugate displayed high chemical stability and photostability.
Highlights ► Pregnant mice were exposed to different BPA doses and its concentration in different organs of the offspring measured. ► The exposure time was from day 1 of gestation until the seventh ...day after delivery. ► Examined organs were liver, muscle, hindbrain and forebrain. ► BPA concentration was found dependent on exposure dose and on the offspring gender. ► The biological significance of the results is discussed.
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